含长烷基吡啶盐氯胺的合成及抗菌性能

Synthesis of long-chained pyridinium N-chloramine for antibacterial applications

摘要:

以4-羟基吡啶为链接单元，通过多步合成策略制备O-烷基化衍生的长链烷基吡啶盐氯胺和N-烷基化衍生的长链烷基吡啶盐氯胺，经NMR和HRMS确证了前体和氯胺结构。以金黄葡萄球菌（S. aureus）和大肠杆菌（E. coli）为模式菌株，以已报道的氯胺{1-[3-（4,4-二甲基-3-氯-2,5-二氧代咪唑烷-1-基）丙基]吡啶-1-鎓氯化物（Ⅱb）}为对照，对所合成氯胺进行了初步抗菌测试。结果表明，对位衍生吡啶盐氯胺抗菌活性明显优于间位衍生氯胺对应物，且抗菌活性随烷基链（—C6H13、—C8H17、—C10H21、—C12H25）增长而显著增强；N-烷基化衍生的长链烷基吡啶盐氯胺的抗菌性能明显优于O-烷基化衍生的长链烷基吡啶盐氯胺。携有—C12H25链吡啶季铵盐氯胺{4-正十二烷氧基-1-[3-(4,4-二甲基-3-氯-2,5-二氧代咪唑烷-1-基)丙基]吡啶-1-鎓氯化物（ⅩⅢd）}和{1-正十二烷基-4-[3-(4,4-二甲基-3-氯-2,5-二氧代咪唑烷-1-基)丙氧基]吡啶-1-鎓氯化物（ⅩⅤe）}分别达到了同系物中最优抗菌活性，活性氯浓度0.056 mmol/L时，ⅩⅢd和ⅩⅤe对金黄色葡萄球菌的lg减少量分别为1.14±0.05和2.74±0.45，对大肠杆菌的lg减少量分别为0.13±0.01、0.53±0.01。氯胺结构与长链烷基吡啶盐结构具有“协同抗菌”效应。

Abstract:

Two types of long-chained pyridinium N-chloramines based on 4-hydroxypyridine were synthesized via poly-step strategy. The structure of precursor and corresponding N-chloramine was confirmed by NMR and HRMS, and antibacterial activity of synthetic N-chloramines was preliminarily tested against E. coli (ATCC 25922) and S. aureus (ATCC 25923) using N-chloramine IIb as control. Antibacterial data showed that the antibacterial activity of para-derivative of pyridinium N-chloramine is superior to that of meta derivative counterpart, and that antibacterial activity showed an increasing trend with the attached chain lengthens. Specifically, the odecyl chained (-C12H25) pyridinium N-chloramine (XIIId/XVe) present the towering antibacterial efficacy, probably due to ‘synergistic’ biocidal action between N-chloramine moiety and long-chained pyridinium center. Besides, N-chloramine XVe derived from N-alkylation exhibits even higher bactericidal activity comparatively, achieving so far the most efficacious N-chloramine antimicrobial.